Calpain is one of the intracellular proteases ubiquitously present in a living body, which is activated by Ca2+. It has been elucidated to this day that abnormal activation of calpain is involved in various diseases such as cerebral apoplexy, subarachnoid hemorrhage, Alzheimer's disease, ischemic disease, muscular dystrophy, cataract, platelet aggregation disorder, arthritis and the like (see Non-patent literature 1).
On the other hand, it has been reported that a calpain inhibitor is effective for maintaining permeability of lens in an experimental cataract model of cultured lens and is useful as a therapeutic agent for cataract, etc. (see Non-patent literature 2, Patent literature 1).
Examples of calpain inhibitors which have been so far reported are peptide halomethane derivatives, peptide diazomethane derivatives, peptidyl aldehyde derivatives, peptidyl α-ketoamide derivatives and the like (for example, see Patent literatures 2 to 6, Non-patent literatures 3 to 4).
(Patent literature 1) WO 93/23032
(Patent literature 2) JP-B-29229/1994
(Patent literature 3) EP-A-0771565
(Patent literature 4) U.S. Pat. No. 6,057,290
(Patent literature 5) JP-A-147564/1998
(Patent literature 6) WO 92/12140
(Non-patent literature 1) Trends in Pharmacological Sciences, vol. 15, page 412, 1994
(Non-patent literature 2) Current Eye Research, vol. 10, Pages 657 to 666, 1991
(Non-patent literature 3) The Biochemical Journal, vol. 253, pages 751 to 758, 1988
(Non-patent literature 4) Journal of Medicinal Chemistry, vol. 35, pages 216 to 220, 1992